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Objective To observe pain behavior and the expression of Fos in the related brain re? gions,including Anterior Cingulate Cortex ( ACC) ,Periaqueductal Gray ( PAG) ,Rostral ventromedial nucle?us ( RVM) in chronic constrictive injury ( CCI) rats and to explore whether ACC modulate spinal nociceptive transmission through endogenous descending facilitatory system. Methods A total of 48 male SD rats were randomly divided into six groups:Naive group,Sham group ( just separated the left sciatic nerves without liga?tion) ,CCI group ( the left sciatic nerve was ligated) ,CCI+P group ( on the 14 th day after surgery,intraper?itoneal injection of 10 mg/kg paroxetine 45 min before behavior test) ,ACC?Sham group ( bilateral microin?jection of 0.9% NaCl in ACC,1μl/each side) and ACC?AP5 group ( bilateral microinjection of AP5 25 mM in ACC,1μl/each side on the 13th day after surgery) . On the 14th day after light?dark transition test,forced swimming test,paw?withdrawal mechanical threshold( PWMT) and paw?withdrawal thermal patency( PWTL) were performed,the rats were terminally anesthetized and ACC,PAG,RVM and the spinal cord was rapidly removed,and then the expression of c?fos was measured by immunohistochemistry. Results ( 1) Rats in CCI group demonstrated nociceptive hypersensitivity and depressive?like behaviors compared with Naive rats, while rats in CCI+P group and in ACC?AP5 group showed less nociceptive hypersensitivity and less depres?sive?like behaviors compared with CCI group. (2)Compared with Naive group,the number of c?fos positive neurons in the bilateral ACC (left,surgery side,4920.6±1053.7;right,2059.3±409.1),VIPAG (9074.8± 2320.3),RVM (6195.4±895.0) and bilateral spinal cord (left,15148.8±3080.2;right,6400.2±1558.4) was significantly enhanced in CCI group, especially in the left side. In contrast, the amount of fos labeled neurons declined in the bilateral ACC (left,2776.4±820.1;right,1120.5±141.4),VIPAG (4002.2± 1171.8),RVM (2938.9±910.3) and bilateral spinal cord (left,8742.0±1131.0;right,3933.1±858.9) in CCI+P group and also declined in the bilateral ACC (left,3623.1±667.4;right,696.5±164.8),VIPAG (5668.8±1403.3),RVM (3972.3±851.7) and bilateral spinal cord (left,10675.4±1725.3;right,3818.3± 1085.1) in ACC?AP5 group. Conclusion Endogenous descending facilitatory system may contribute to ACC modulating spinal nociceptive transmission.
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Objective To investigate the effect and mechanism of calcitonin(CT) in glutamate release from primary cultured neurons of midbrain periaqueductal gray matter(PAG).Methods Primary dissociated culture of PAG neurons was prepared from neonatal Sprague-Dawley (SD) rats.The cultured cells were divided into 4 groups:control group,salmon calcitonin (sCT) group,CT antagonist group (sCT8-32),and protein kinase C (PKC) inhibitor chelerythrine(Che) group.Each group was further divided into subgroups representing low,middle,and high levels of drugs.Glutamate release from the cultured PAG neurons evoked by sCT and/or other interfering factors was detected by using high-performance liquid chromatography (HPLC) assay.Results (1) Compared with the control group,sCT group yielded a time-dependent and concentration-dependent glutamate release from the cultured PAG neurons,and the most effective concentration of sCT was 20 nmol/L(P＜0.01).(2) sCT8-32,a selective antagonist of CT receptor,significantly reversed the effect of 20 nmol/L sCT on glutamate release from cultured PAG neurons,and the most effective concentration was 100nmol/L sCT8-32 (P＜0.01).(3) Incubation of the cultured neurons with Che inhibited the glutamate release from cultured PAG neurons evoked by 20 nmol/L sCT,and 100 μmol/L Che was most effective(P＜0.01).Conclusion CT receptors participates in the glutamate release from PAG neurons in which intracellular protein kinase C signaling pathway is involved.
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Objective To explore the effect of Electroacupuncture on anxiety mood and periaqueductal grey (PAG) β-endorphine expression in rats with morphine abstinence syndrome.Methods The model of heroin-addicted rat was firmly established by the subcutaneous injection of gradually-increased dosages of heroin. Rats were randomly divided into control group, herion-addict group, withdrawal group, electroacupuncture group.Anxiety mood of experimental rats were assessed by Elevated Plus Maze test. Expression of β-EP in PAG was detected by immunohistochemstry. The effect of electroacupuncture at bilateral zusanli and sanyinjiao on anxiety mood and expression of β-EP in PAG was observed in rats with herion abstinence symptom.Results The anxiety index in rats with herion abstinence symptom:the value of OT％,OE％and head-dips times was (12.5±4.3) ％, (17.1±6.7)％and (5.7±2.0) times respectively,lower than that in control group [ (26.8±8.7) ％,(32.4±6.0) ％ and (12.2±4.0) times respectively],there existed significant difference(The value of P was 0.003,0.018 and 0.003 respectively).Meanwhile,The expression of β-EP-positive neurons(206.1±23.1)was significantly higher than the control(186.2±15.3). There existed significant difference( P =0.041).Electroacupuncture could increase OT％,OE％,head-dips times[(26.5±8.7)％、(31.8±7.7)％ and (9.9±3.1) times respectively] in rats with herion abstinence symptom,which comparied with control group were not statistically distinctive(The value of P was 0.920,0.816 and 0.122 respectively).The expression of β-EP(185.3±11.4)in PAG increased, which comparied with control group(186.2±15.3)were not statistically distinctive( P =0.891).Conclusion Electroacupuncture could inhibit the abstinence syndrome effectively.And there is obvious promotion of β-EP expression in PAG. This is probably one of underlying mechanisms for electroacupuncture improving withdrawal symptoms.
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@#Objective To investigate the involvement of sympathetic nerve system in the transmission of nociceptive information related to vascular headache. Methods Fos expression in the midbrain periaqueductal grey (PAG) induced by electrical stimulation of dural matter near the superior sagittal sinus (SSS) of the rat was determined before and after the extirpation of the superior cervical ganglion (SCG) using standard avidin-biotin immunohistochemistry. Results Fos immunoreactive positive neurons were detected in the ventrolateral PAG, and were bilateral symmetry. Fos expression was (133.3±12.5) in SCG extirpated group, and higher than that in sham-operated group (76.0±11.3). Conclusion The sympathetic system may be involved in the transmission of nociceptive information through PAG, associated with vascular headache such as migraine.
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The paper reviews mechanisms underlying autonomic disorders, with a focus on cardiovascular dysfunction. Neurosurgical approaches are described for medically refractory hypertension and orthostatic hypotension. After review of microvascular decompression of the rostral ventrolateral medulla, stereotactic CT and MRI guided deep brain stimulation of the periaqueductal grey matter (PAG) is evaluated. Results are presented from patient studies showing reductions in blood pressure with ventral PAG stimulation and increases in blood pressure with dorsal PAG stimulation. A rationale for the treatment of autonomic disorders by neurosurgical intervention is discussed.
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Investigamos o possível efeito das espermina e receptores das poliaminas na substância cinzenta periaquedutal dorsal, sobre a ansiedade. Grupos de ratos receberam microinjeções de espermina (2,5 nmol) no interior da matéria cinzenta periaquedutal dorsal e foram testados no labirinto em cruz elevado. Os resultados indicam um aumento significativo na porcentagem de entradas e no tempo de permanência nos braços abertos. Outro experimento mostra que o efeito ansiolítico obtido após microinjeção de espermina (2,5 nmol) no interior da matéria cinzenta periaquedutal dorsal, foi bloqueado pela microinjeção prévia dos antagonistas das poliaminas, arcaina (4 nmol) ou ifenprodil (5 nmol), neste sítio. Estes resultados indicam que o receptor da espermina interage na modulação da ansiedade em ratos expostos ao labirinto em cruz elevado. Considerando que as poliaminas são encontradas normalmente no cérebro, estes resultados sugerem que o sistema de poliaminas na matéria cinzenta periaquedutal dorsal possuem um importante papel na ansiedade
To investigate a possible effect of the spermine and its polyamins receptors in the dorsal periaqueductal grey (DPAG) in anxiety. Groups of rats received microinjections of spermine (2.5 nmol) into DPAG and were tested in the elevated plus-maze apparatus. Results indicated an overall significant increase in the percentage of entries and in the time spent in open arms. In another experiment the anxiolytic effect obtained after the microinjection of spermine (2.5 nmol) into DPAG was block by previous microinjection of polyamines antagonists, arcaine (4 nmol) or ifenprodil (5 nmol) into the same site. These results indicate that the spermine receptor interaction in the modulation of anxiety in rats exposed to the elevated plus-maze. Considering that polyamines are natural component of the brain, these results suggest that polyamine system within DPAG may play a role in aversion and anxiety
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Rats , Anxiety , Periaqueductal Gray , Polyamines , SpermineABSTRACT
Objective To investigate the role of PAG in migraine Methods A transformed superior sinus stimulation migraine model was applied to observe Fos expression and co localization of 5 HT with Fos in PAG following the stimulation of dual matter adjacent to the superior sagittal sinus in rats Results 5 HT immunoreactive neurons, densely located in ventrolateral and ventromedial sectors, were found throughout the PAG Fos like immunoreactivity neurons were obviously increased in stimulated group than in unstimulated and control groups The double labelled neurons accounted for 15 0%?2 8% of 5 HT immunoreactive neurons and 24 0%?4 3% of Fos like immunoreactivity The double labelled population mainly distributed in ventrolateral sector Conclusions It suggests that neurons in PAG, especially in ventrolateral sector in caudal segment, might be excited in migraine model of rat The excited cells and 5 HTnic neurons might have a similar distribution pattern in PAG, with part of excited cells being 5 HTnic neurons Other types of excited neurons and the subtype of 5 HT receptor were not included in the experiment, and would be studied further as to getting a better understanding of the pathophysiology of migraine
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Objective To investigate the effect of intra-periaqueductal grey(PAG) injection of calcitonin gene-related peptide(CGRP) on antinociception in rats with inflammation.Methods Subcutaneous injection of 0.1 mL of 2% carrageenan into the plantar region of the left hindpaw,after which,the effect of intra-periaqueductal grey injection of calcitonin gene-related peptide on the hindpaw withdrawal latency to thermal stimulation and hindpaw withdrawal threshold to mechanical stimulation was observed.Results(1) Subcutaneous injection of 0.1 mL of 2% carrageenan into the plantar region of the left hindpaw induced a significant increase in the volume of the ipsilateral hindpaw,and a significant bilateral decrease of the hindpaw withdrawal latency to thermal stimulation and hindpaw withdrawal threshold to mechanical stimulation.(2) Intra-periaqueductal grey injection of 0.26 nmoL or 0.52 nmoL of CGRP,instead of 0.13 nmoL induced a significant increase of the hindpaw withdrawal latency to thermal stimulation and hindpaw withdrawal threshold to mechanical stimulation.Conclusion CGRP in periaqueductal grey was involved in antinociception in rats.